conspectus of disease
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Chapter 1. conspectus of disease
Yu-Hong Jia, Ph.D
Department of pathophysiology
Dalian medical university
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• concept of disease• etiology of diseas• pathogenesis of disease• outcome of disease.
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1. Concept of disease
• Disease: is referred as aberrant manifestation of deregulated homeostasis caused by harmful agents in a certain condition.
•A certain condition
•Cause of disease
•The interation of damage and anti-damage
•A series of funtional, metabolic and structural alterations in the body
•Clinical Signs and symptoms
Cold, low resistance
Flu virus
Increased immunoresponse
Changes of Glucose, fat and protein metabolism
Alteration of cardiopulmonary function
Catarrh(nose running,sneeze,)Cough, fever,
Flu
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Health Former definition of health:The state of the organism when it functionsoptimally without any evidence of disease.
Definition of health from WHO: Health indicates not only without any evidence of disease, but also a state of complete well- being physically, psychologically and socially.
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Sub-health
• A situation in which the person does not show specific symptoms and signs of illness, but lives a low-quality of life both physically and mentally.
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2. Etiology of disease.
Contributing factors that cause disease.
Causative factors
Predisposing factors
Precipitating factors
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• Extrinsic factors• Intrinsic factors
(1) Causes of disease (causative factors)
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– Biological agents: microorganisms and
parasites– Chemical agents: non-specific or specific– Physical agents: mechanical injuries,
extremes of temperature, electricity and radiation. Participate in initiation but not development of disease. Non-specific injury.
– Nutritional imbalance: excesses or deficiencies of nutrients.
• Extrinsic causes
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• Intrinsic factors
– Genetic factors: single or polygenic mutation– Congenital factors: abnormal embryonic
developmental error– Immunological factors: the immune response is
deficient or inappropriately strong or misdirected– Psychological factors: Anxiety, strong or persistent psychological stress.
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(2) Predisposing factor
• influence the susceptibility or resistance to certain disease.– Genetic constitution – Physiological diathesis– Psychological characteristics
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(3) Precipitating factor
• intensify the roles of causative factors and promote the onset and development of diseases.– Natural condition e.g. weather condition,
geographical environment– Physical condition e.g. physical or mental
fatigue or anxiety– Social condition e.g. poor labor and hygiene
condition
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• Pathogenesis of disease refers to the rules and mechanisms underlying the development or evolution of the disease.– General rules for pathogenesis of disease– Fundamental mechanisms for disease
3. Pathogenesis of disease
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(1) General rule for pathogenesis of disease
1) Disruption of homeostasis2) Process of damage and anti-damage3) Reversal rule of cause and result4) Correlation between systemic and local
regulations
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1) Disruption of homeostasis
• Homeostasis denotes the process whereby the internal environment of an organism tends to remain balanced and stable, which is required for optimum functioning.
• Disruption of homeostasis by harmful agnents may cause disease.
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2) Process of damage and anti-damage
• Any disease is a process full of battle between damage and anti-damage.
• The contrast between strength of damage and anti-damage determine the development of a disease.
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reninangiotensinogen
Angiotensin ⅠAngiotensin Ⅱ
Increased water and sodium reaborption
↑effective circulatory blood volume
hemorrhage
↓effective circulatory blood volume
↓Renal artery pressure
↓GFR→↓Na+ at macula
densa
↑Sympathetic nerve
glomerulus
Juxtaglomerular cells
Converting enzyme
+
Organ ischemia, dysfunction
damage
(JG cells)
Adrenal cortex
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3) Reversal rule of cause and result
Primary Primary causecause
Result Result (cause)(cause)Further Further alteration alteration
Secondary Secondary alterationalteration
(cause)(cause)
(+)(-)
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Severe hemorrhage
↓Cardiac output
↓Blood pressure
↑Symphathetic nerve
↑catecholamine
Constriction of Microartery & micro
vein
Tissue hypoxia
acidosisRe-open of
capillaryBlood stagnant in microcirculation
↓Blood volume returned to heart
+
↓↓BP
v i co
us
i
c yc l e
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4) Correlation between systemic and local regulations
Systemic alteration
Local alteration
disease
Neural-humoral regulation
Neural-humoral regulation
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Furuncle, Local
inflammation
Systemic reaction of fever and elevated
leukocyte
Systemic metabolic disorder caused by diabetes mellitus
furuncle
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(2) Fundamental mechanisms for diseases
1) Neural mechanism2) Humoral mechanism3) Cellular mechanism4) Molecular mechanism
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• Alteration of neural system is tightly related with pathogenesis of disease.
• The alterations of neural system induced by pathogens include:– Direct injury of neural system (e.g. type B encephalitis)– Change of neural reflex (e.g. Parkinson’s disease)– Change of metabolism of neural cells (e.g. Alzheimer’s
disease)• Among neural mechanism, sympathetic system is
of important role.– Sympathetic nerve participates in many pathologic
processes, e.g. edema, stress, shock
1) Neural mechanism
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Sympathetic system Distribution of sympathetic system• Organs of head, neck, trunk, & external genitalia• Adrenal medulla• Sweat glands in skin• Arrector muscles of hair• All vascular smooth muscle
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2) Humoral mechanism
• Humoral dysfunction indicates the alterations in number and activities of some humoral factors.
• Humoral factors include:– Hormones (i.e. Renin-Angiotensin-Aldosterone system, A
DH)– Chemical mediators (i.e. histamine, prostaglandin)– Cytokines (i.e. interleukines, tumor necrosis factors)
• Function manner of humoral factors include:– Endocrine– Paracrine– Autocrine– intracrine
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Decreased blood pressure
Angiotensin Ⅰ
Angiotensin Ⅱ
Aldosterone
Decreased urine volume conserves blood pressure
Renin
Regulation of Renin-Angiotensin-Aldosterone system
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OsmoreceptorsIncreased osmotic press
ure
Baroreceptors (aortic arch, carotid sinus) Decrease
blood pressure
Neurosecretory cell
Posterior pituitory
vasoconstriction
Blood vessel
Increased blood volume and
increased blood pressure
kidney
Increased reabsorption of water
ADH
Regulation and effect of ADH
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Endocrine action: the hormone is distributed in blood and binds to distant target cells.Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood.Autocrine action: the hormone acts on the same cell that produced it.
Manners with which humoral factors exerts its function
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Neural-humoral regulation
endocrine glands
neural system
one loop of neural system
effect
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• For example:Sympathetic nerve excites→increased secretion of epinephrine and norepinephrine by medulla of adrenal gland → α、 ß receptors excitation in cardiac vascular system → heart rate↑ and blood vessels contract → BP↑
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3) Cellular mechanism
• Cell damage – Some pathogens destroy the cells with no selection, i.e. strong
acid and alkali– Others attack cells selectively, i.e. hepatitis virus
• Selective damage of cells involves: cell membrane Na+ pump( Na+-K+-ATPase) → cellular edema Ca2+ pump(Ca2+-ATPase) → Ca2+ overload
organelles mitochondrium→ ATP↓ lysosome→ cell autolysis
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4) Molecular mechanism
• abnormal alteration at molecular level – macro-molecule →nucleic acid, protein
• Molecular disease• i.e. sickle cell anemia
– micro-molecule
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4. Outcome of disease.
• Recovery– Complete recovery : the pathological
alterations are perfectly restored and the signs and symptoms of disease disappear entirely.
– Incomplete recovery: the main symptoms disappear but some pathological changes are still there.
• i.e. myocardial infarction
• Death
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Death
• The body as a whole stop working forever• The cessation of heartbeats was used as c
riterion of death before.• The accepted definition of death now is br
ain death.
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Brain Death (WHO criteria)
• Cessation of spontaneous respiration• Irreversible coma• Absence of cephalic reflexes• Dilated or fixed pupils• Absence of any electrical activity of the
brain• Absence of brain blood flow
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Significance for diagnosis of brain death
In favor of recording the time of death
Define the time to terminate for the rescue
In favor of organ transplantation
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review• Concept of disease
– Disease※, health, sub-health• Etiology of disease
– Causative factors– Predisposing and precipitating factors
• Pathogenesis of disease– General rule
• Disruption of homeostasis• Damage and anti-damage• Alternation of cause and result• Correlation of System and local
– Fundamental mechanism• Neural mechanism• Humoral mechanism• Cellular mechanism• Molecular mechanism
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• The alterations of neural system – Direct injury of neural system, i.e.
• Type B encephalitis– Change of neural reflex and metabolism of neura
l cells, i.e. • Exciting of sympathetic nerve → release of catechola
mine→biological effects; • Alzheimer’s disease →β-amyloid peptide accumulatio
n in brain cell
1) Neural mechanism
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• alterations in number and activities of humoral factors.– Hormones (i.e. Renin-Angiotensin-Aldosterone sy
stem, ADH)– Chemical mediators (i.e. histamine, prostaglandi
n)– Cytokines (i.e. interleukines, tumor necrosis facto
rs)
2) Humoral mechanism
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• Function manner of humoral factors include:– Endocrine– Paracrine– Autocrine– intracrine
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3) Cellular mechanism
• Cell damage– cell membrane
• Na+ pump• Ca2+ pump
– Cell organelles• Mitochondrium• lysosome